Hearing problems can result from a variety of disorders, diseases or traumas of the inner ear. Symptoms of inner ear problems include, but are not limited to, hearing loss, dizziness, vertigo and tinnitus. Several inner ear diseases have recently been classified as autoimmune diseases. These include, but are not limited to, Meniere's disease, progressive bilateral sensorineural hearing loss (PSHL), otosclerosis and sudden hearing loss.
Meniere's disease, although idiopathic by definition, has been ascribed to a variety of causes, among which are autoimmune factors. There is evidence to suggest that antibodies generated against inner ear proteins cause inner ear inflammation and swelling that can result in a complete loss of hearing (Dereby, M. Otolaryngology-Head & Neck Surgery 114:360-365, 1996). Symptoms typically associated with Meniere's disease include ringing in the ears, dizziness, a sense of fullness or pressure in the ears, and progressive deafness. These symptoms may be produced by a sudden influx of fluid into the endolymphatic sac, resulting in a rupture of Reisser's membrane in the cochlea. Immunological derangement of the endolymphatic sac or other membranous structures of the inner ear could initiate a cascade of reactions leading to endolymphatic hydrops and presenting as Meniere's disease (Soliman, A. American Journal of Otology 17:70-80, 1996). There are at least four million Meniere's disease patients in the United States, and many more patients report symptoms associated with Meniere's disease but cannot be positively diagnosed.
Researchers have attempted to isolate the antigen or antigens responsible for autoimmune inner ear diseases. A protein is considered to be a potential antigen if it is reactive with antibodies produced by patients exhibiting autoimmune inner ear diseases.
For example, antibodies in the sera of patients having inner ear disease have been found to react with protein bands of 58 kD and of 30 kD on Western blots of guinea pig inner ear extracts (Cao, M. et al., Laryngoscope 106:207-212, 1996). The 58 kD band was shown to be nonspecific to the inner ear when antibodies reacted with a 58 kD band on Western blots of guinea pig brain, lung and liver. In contrast, the 30 kD band was specific to the inner ear. Antibodies from patients reacted with a 30 kD band on Western blots of extracts from Corti's organ, the spiral ganglion and the acoustic nerve fiber, but not with extracts from the spinal ligament and the stria vascularis.
Antibodies against a 30 kD cochlear protein have been in reported in the serum of some patients with Meniere's disease (Joliat, T. et al., Ann. Otol. Rhinol. Laryngol. 101:1001-1006, 1994 and Cao, M. et al., Laryngoscope 106:207-212, 1996). This 30 kD protein has been identified as the major peripheral myelin protein "PO" and is believed to be associated with acoustic nerve and spiral ganglion (Cao, M. et al., Laryngoscope 106:207-212 (1996). Antibodies reactive with the 30 kD protein are not specific for Meniere's disease as these antibodies have been found in patients having other autoimmune diseases such as progressive bilateral sensorineural hearing loss (PSNHL), otosclerosis and sudden deafness and in control subjects. (Cao, M. et al., IMMUNOBIOLOGY IN OTOLOGY, RHINOLOGY AND LARYNGOLOGY (eds. Mogi, G., Veldman, J., and Kawauchi, H.) Kugler Publ. Amsterdam/N.Y., (1994) pp. 263-268).
Antibodies against a 68 kD protein in extracts from bovine inner ear have been reported in the serum of PSNHL patients (Harris J. and Sharp P. Laryngoscope 100:516-524, 1990). This 68 kD protein has been identified as a 70 kD heat shock protein that has been implicated in other autoimmune diseases such as Lyme's disease and ulcerative colitis (Billings P. et al. Ann. Otol. Rhinol. Laryngol. 104:181-188, 1995).
An early diagnosis of autoimmune inner ear disease is critical. Prompt treatment of the disease at an early stage of the illness may preserve any remaining inner ear function. Moreover, the ability to distinguish antigenic epitopes of the inner ear relevant to the pathogenesis of specific autoimmune inner ear diseases will enable clinical investigation and research on autoimmune inner ear disease, and will further enable the clinical diagnosis of autoimmune inner ear diseases and immunologic therapy.
As the availability of human inner ear tissue is extremely limited, there is an on-going need for the identification of disease-specific antigens and for the development of simple, sensitive and reproducible assays for the detection and differential diagnosis of autoimmune inner ear diseases.